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. 2024 May 2:14:1394648.
doi: 10.3389/fonc.2024.1394648. eCollection 2024.

Survival after allogeneic transplantation according to pretransplant minimal residual disease and conditioning intensity in patients with acute myeloid leukemia

Claudia Núñez-Torrón Stock  1   2   3 , Carlos Jiménez Chillón  4 , Fernando Martín Moro  5 , Juan Marquet Palomanes  5 , Miguel Piris Villaespesa  5 , Ernesto Roldán Santiago  6 , Eulalia Rodríguez Martín  6 , Anabelle Chinea Rodríguez  5 , Valentín García Gutiérrez  2   5 , Gemma Moreno Jiménez  5 , Javier López Jiménez  2   5 , Pilar Herrera Puente  2   5
Affiliations

Survival after allogeneic transplantation according to pretransplant minimal residual disease and conditioning intensity in patients with acute myeloid leukemia

Claudia Núñez-Torrón Stock et al. Front Oncol. .

Abstract

Background: The measurement of minimal residual disease (MRD) by multiparametric flow cytometry (MFC) before hematopoietic stem cell transplantation (HSCT) in patients with acute myeloid leukemia (AML) is a powerful prognostic factor. The interaction of pretransplant MRD and the conditioning intensity has not yet been clarified.

Objective: The aim of this study is to analyze the transplant outcomes of patients with AML who underwent HSCT in complete remission (CR), comparing patients with positive MRD (MRD+) and negative MRD (MRD-) before HSCT, and the interaction between conditioning intensity and pre-HSCT MRD.

Study design: We retrospectively analyzed the transplant outcomes of 118 patients with AML who underwent HSCT in CR in a single institution, comparing patients with MRD+ and MRD- before HSCT using a cutoff of 0.1% on MFC, and the interaction between conditioning intensity and pre-HSCT MRD.

Results: Patients with MRD+ before HSCT had a significantly worse 2-year (2y) event-free survival (EFS) (56.5% vs. 32.0%, p = 0.018) than MRD- patients, due to a higher cumulative incidence of relapse (CIR) at 2 years (49.0% vs. 18.0%, p = 0.002), with no differences in transplant-related mortality (TRM) (2y-TRM, 19.0% and 25.0%, respectively, p = 0.588). In the analysis stratified by conditioning intensity, in patients who received MAC, those with MRD- before HSCT had better EFS (p = 0.009) and overall survival (OS) (p = 0.070) due to lower CIR (p = 0.004) than MRD+ patients. On the other hand, the survival was similar in reduced intensity conditioning (RIC) patients regardless of the MRD status.

Conclusions: Patients with MRD+ before HSCT have worse outcomes than MRD- patients. In patients who received MAC, MRD- patients have better EFS and OS due to lower CIR than MRD+ patients, probably because they represent a more chemo-sensitive group. However, among RIC patients, results were similar regardless of the MRD status.

Keywords: acute myeloid leukemia; allogeneic transplantation; conditioning intensity; minimal residual disease; monosomal karyotype.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

Figure 1
Figure 1
Event-free survival and overall survival according to minimal MRD status by MFC before HSCT. Estimates of (left) EFS and (right) OS after HSCT for patients with AML in complete remission according to the MRD status, shown individually for MRD− (n = 86) and MRD+ (n = 32), respectively. Patients with MRD− have significantly worse EFS (2y-EFS 56.5% vs. 32.0%) with no significant differences for OS (2y-OS was 60.0% vs. 53.5%). EFS, event-free survival; HSCT, hematopoietic stem cell transplantation; MRD, minimal residual disease; OS, overall survival.
Figure 2
Figure 2
Event-free survival and overall survival according to conditioning intensity. Estimates of (left) EFS and (right) OS after HSCT for patients with AML in complete remission according to conditioning intensity, shown individually for MAC (n = 70) and RIC (n = 48), respectively. Patients with MAC− have a trend toward better EFS (2y-EFS, 54.0% vs. 43.0%) and significantly better OS (62.0% vs. 51.5%). EFS, event-free survival; HSCT, hematopoietic stem cell transplantation; MAC, myeloablative conditioning; OS, overall survival; RIC, reduced intensity conditioning.
Figure 3
Figure 3
Event-free survival and overall survival according to the MRD status before HSCT and stratified by conditioning intensity. Estimates of (upper left) EFS and (upper right) OS after HSCT for patients with AML in complete remission according to the MRD status before HSCT among patients who received MAC, shown individually for MRD− (n = 51) and MRD+ (n = 19), respectively. Patients with MRD− have significantly better EFS (2y-EFS, 63.0% in MRD− vs. 31.5.0% in MRD+) and a trend to better OS (2y-OS, 67.0% vs. 50.5%) than patients with MRD+. Estimates of (lower left) EFS and (lower right) OS after HSCT for patients with AML in complete remission according to the MRD status before HSCT among patients who received RIC, shown individually for MRD− (n = 35) and MRD+ (n = 13), respectively. Patients have similar EFS (2y-EFS, 47.0% for MRD− vs. 33.0% for RIC) and OS (2y-OS, 49.0% vs. 58.0%) regardless of conditioning intensity. EFS, event-free survival; HSCT, hematopoietic stem cell transplantation; MRD, minimal residual disease; MAC, myeloablative conditioning; OS, overall survival; RIC, reduced intensity conditioning.
Figure 4
Figure 4
Estimated cumulative incidence of relapse and transplant-related mortality according to the MRD status before HSCT. Estimates of (left) CIR and (right) TRM after HSCT for patients with AML in complete remission according to the MRD status, shown individually for MRD− (n = 86) and MRD+ (n = 32), respectively. Patients with MRD+ had a significantly higher 2y-CIR (49.0%) compared to 18.0% in MRD− patients with no differences in 2y-TRM (19.0% and 25.0%, respectively). CIR, cumulative incidence of relapse; HSCT, hematopoietic stem cell transplantation; MRD, minimal residual disease; TRM, transplant-related mortality.
Figure 5
Figure 5
Estimated cumulative incidence of relapse and transplant-related mortality according to conditioning intensity. Estimates of (left) EFS and (right) OS after HSCT for patients with AML in complete remission according to conditioning intensity, shown individually for MAC (n = 70) and RIC (n = 48), respectively. Patients have similar CIR (2y-CIR, 24.5% for MAC and 30.0% for RIC) and TRM (2y-TRM, 21.0% vs. 27.0%) regardless of conditioning intensity. CIR, cumulative incidence of relapse; HSCT, hematopoietic stem cell transplantation; MAC, myeloablative conditioning; RIC, reduced intensity conditioning; TRM, transplant-related mortality.
Figure 6
Figure 6
Estimated cumulative incidence of relapse and transplant-related mortality according to the MRD status before HSCT and stratified by conditioning intensity. Estimates of (upper left) CIR and (upper right) TRM after HSCT for patients with AML in complete remission according to the MRD status before HSCT among patients who received MAC, shown individually for MRD− (n = 51) and MRD+ (n = 19), respectively. Patients with MRD− have significantly lower CIR (2y-CIR, 15.0% in MRD− vs. 47.5% in MRD+) with no differences in TRM (2y-TRM, 21.5% vs. 21.0%) compared to MRD+. Estimates of (lower left) CIR and (lower right) TRM after HSCT for patients with AML in complete remission according to the MRD status before HSCT among patients who received RIC, shown individually for MRD− (n = 35) and MRD+ (n = 13), respectively. Patients had no statistically significant differences for both CIR (2y-CIR, 21.5% for MRD− vs. 52.0% for RIC) and TRM (2y-TRM, 31.0% vs. 15.0%). CIR, cumulative incidence of relapse; TRM, transplant-related mortality; HSCT, hematopoietic stem cell transplantation; MRD, minimal residual disease; MAC, myeloablative conditioning; OS, overall survival; RIC, reduced intensity conditioning.
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